Bioorg. Med. Chem., 5, 437(1997) describes that the 2-(N-methyl-N-methanesulfonylamino)pyrimidine compound is employable as an intermediate compound for producing a cholesterol reducing agent (HMG-CoA reductase inhibitor: S-4522) having the following formula:
and which is now generally known as the calcium salt of rosuvastatin or rosuvastatin calcium.
WO 01/04100 describes a process for preparing the 2-(N-methyl-N-methanesulfonylamino)pyrimidine compound which comprises the steps of:
reacting methyl isobutyrylacetate with 4-fluoro-benzonitrile to produce methyl 2-[l-amino-1-(4-fluoro-phenyl)methylene]-4-methyl-3-oxopentanate; and
reacting the 2-[1-amino-1-(4-fluorophenyl)methyl-ene]-4-methyl-3-oxopentanate with N-cyano-N-methyl-methanesulfonamide which is obtained by reaction between N-methylmethanesulfonamide and cyanogen chloride, to produce 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(N-methanesulfonyl-N-methylamino)pyrimidine.
It is described that the total yield (based on the amount of methyl isobutyrylacetate) is 45.5%.
It appears that the process described in WO 01/04100 is disadvantageous for the industrial preparation, because the yield is not high and it is necessary to employ toxic cyanogen chloride as one of the starting compounds.
Accordingly, it is an object of the invention to provide a novel process for preparing a 2-(N-methyl-N-methanesulfonylamino)pyrimidine or an analogous amino-pyrimidine compound thereof, more particularly to provide a novel process which provides the compound more conveniently and/or without employing a toxic compound and/or provides the compound in high yield and/or high purity.
It is another object of the invention to provide a novel process for preparing a 2-(N-methyl-N-methanesulfonylamino)pyrimidine compound or an analogous amino-pyrimidine compound thereof which is favorably employable in the industrial preparation.